Prior to bone marrow transplantation (BMT) titres of IgG antibodies for cytomegalovirus (CMV), herpes simplex virus (HSV) and varicella zoster virus (VZV) were analysed in 51 donors and recipients of allogeneic bone marrow. Donor mononuclear cells from peripheral blood and bone marrow cells were stimulated with antigen prepared from CMV, HSV and VZV. High IgG titres for HSV in the recipient were associated with grade II-III acute graft-versus-host disease (GVHD) (P = 0.05). Furthermore, the combination of positive IgG titre for HSV antibodies in the recipient, and strong donor blood mononuclear cell reactivity to HSV antigen in HSV immune donors, significantly increased the incidence of grade II-III acute GVHD (P = 0.04). The data suggest that HSV immune donor mononuclear cells may initiate a GVH reaction.